PHEX p.Ser373=
c.1119C>T · rs753296824 · VCV2174301
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.105%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.20 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.99 | GERP 0.76, phastCons 1 |
| Overall | ||
| CADD | 9.857 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.105%
Admixed American · 48/45,831 alleles
Filtering AF
0.0812%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0728%
Overall
0.00455%
55/1,209,029 alleles · rare
exomes 49/1,096,497 · genomes 6/112,532 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.105% | 955 |
| Remaining individualsnot grpmax-eligible | 0.00631% | 15,859 |
| European (non-Finnish) | 0.000447% | 223,477 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PHEX
- Protein
- p.Ser373=
- Coding
- c.1119C>T
- MANE Select
- NM_000444
- dbSNP
- rs753296824
- Type
- single nucleotide variant
- Location
- chrX:22111506 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 373
- the peptidase m13 domain
Similar variants
- PHEX c.1079+1G>A Pathogenic ★★ same type
- PHEX c.1079+2T>G Pathogenic ★★ same type
- PHEX c.1080-1G>A Pathogenic ★★ same type
- PHEX c.1080-2A>G Pathogenic ★★ same type
- PHEX c.1080-3C>G Pathogenic ★★ same type
- PHEX c.1173+1G>A Pathogenic ★★ same type
- PHEX c.1173+2T>C Pathogenic ★★ same type
- PHEX c.1173+5G>C Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/phex-p-ser373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown